The Shiga toxin B subunit (STxB), which is involved in cell membrane attachment and trafficking of Shiga holotoxin, binds specifically to the glycosphingolipid Gb3. In biological membranes, Gb3 glycosphingolipids differ in their fatty acid composition and there is strong evidence that the fatty acid alters the binding behavior of STxB as well as the intracellular routing of the Shiga toxin/Gb3 complex. By means of chemical synthesis, Gb3 species with different fatty acids as well as fluorescently labeled compounds have become accessible enabling us to investigate the influence of the fatty acid on the partition of Gb3 in liquid-ordered (lo)/liquid-disordered (ld) phase-separated lipid bilayers and how this partition influences Shiga toxin binding. Three different model membrane systems were applied, namely giant unilamellar vesicles, supported lipid bilayers as well as pore-spanning membranes. Our results obtained using the different model membrane systems clearly demonstrate that the fatty acid of Gb3 significantly impacts the overall phase behavior of the membranes. Moreover, the lateral organization of STxB bound to the membranes is influenced by the Gb3 species, which is discussed in the context of Shiga toxin induced invaginations and its internalization into the cell.

Fatty acids of Gb3 influence its partition in phase separated lipid membranes as well as Shiga toxin binding

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.